Control of neural modulation therapy using cervical impedance

ABSTRACT

An implantable apparatus can comprise an electrical test energy delivery circuit configured to provide an electrical test signal to a cervical location in a patient body. A detector circuit can use the electrical test signal to detect cervical impedance and generate a cervical impedance signal representing fluctuations in the detected cervical impedance. The implantable apparatus can comprise a therapy delivery circuit, such as configured to provide electrical neural modulation therapy using a neural modulation timing parameter, and a processor circuit that can be coupled to the electrical test energy delivery circuit, the detector circuit, and the therapy delivery circuit. The processor circuit can be configured to determine a pulsatile signal or pulse pressure signal, such as using the cervical impedance signal, identify a characteristic of the pulsatile signal or pulse pressure signal, and control a neural modulation therapy using the timing parameter and the identified pulse pressure signal characteristic.

CLAIM OF PRIORITY

This application is a continuation of U.S. application Ser. No.13/761,372, filed Feb. 7, 2013, now issued as U.S. Pat. No. 8,812,130,which claims the benefit of priority under 35 U.S.C. §119(e) of Stahmannet al., U.S. Provisional Patent Application Ser. No. 61/595,745,entitled “CONTROL OF NEURAL MODULATION THERAPY USING CERVICALIMPEDANCE”, filed on Feb. 7, 2012, each of which is herein incorporatedby reference in its entirety.

BACKGROUND

Neural stimulation, such as vagus nerve stimulation, has been proposedas a therapy for a number of conditions. Examples of neural stimulationtherapies include neural stimulation therapies for respiratory problemssuch as sleep disordered breathing, blood pressure control such as totreat hypertension, cardiac rhythm management, myocardial infarction andischemia, heart failure (HF), epilepsy, depression, pain, migraines,eating disorders and obesity, and movement disorders.

OVERVIEW

Some embodiments, by way of example and not limitation, provide animplantable apparatus. For example, the implantable apparatus caninclude an electrical test energy delivery circuit and a detectorcircuit. The electrical test energy delivery circuit can be configuredto provide a non-neurostimulating electrical test signal to a cervicallocation in a patient body (e.g., at or near a patient neck region),such as using an implanted electrode. The detector circuit can beconfigured to use the electrical test signal to detect cervicalimpedance or to generate a cervical impedance signal representingfluctuations in the detected cervical impedance over time. Thefluctuations in the detected cervical impedance can correspond todimensional changes of a blood vessel, such as a carotid artery orjugular vein. Such fluctuating, dimensional changes can be used todetermine pulsatile information, which is information related to cardiacactivity and/or information related to the pulsing blood through thepatient's cardiovascular system. For example, the cervical impedance canbe used to determine one or more physiological parameters, such as heartrate, phases of a blood pressure cycle, phases of a cardiac cycle, apulse transit time, relative pulse pressure, or arterial compliance,among others. In some examples, these and other parameters can be usedto monitor a patient health status or to modulate a patient therapy,among other uses.

In an example, the implantable apparatus can comprise a therapy deliverycircuit configured to provide electrical neural modulation therapy to apatient using an implanted electrode and a neural modulation timingparameter. In an example, the implantable apparatus can comprise aprocessor circuit, such as can be coupled to an electrical test energydelivery circuit, a detector circuit, and a therapy delivery circuit.The processor circuit can be configured to determine pulsatileinformation from a cervical impedance signal, identify at least onefeature of the pulsatile information, and control delivery of a neuralmodulation therapy using the neural modulation timing parameter and theat least one identified feature of the pulsatile information from thecervical impedance signal.

Various embodiments can be used to identify an appropriate, orbeneficial, delivery time for neural modulation therapy, such as can beused to mimic or enhance a natural patient physiological response.Various embodiments use cervical impedance information, such as a changein cervical impedance, to identify a pulsatile signal, or a bloodpressure change in a blood vessel, and initiate or adjust a neuralmodulation therapy in response to the identified signal or pressurechange. Various embodiments use one or more features of a cervicalimpedance or pulsatile signal (e.g., a local peak of a signal waveform)to adjust a neural modulation therapy parameter, such as a neuralmodulation therapy timing parameter.

This overview is intended to provide an overview of some of theteachings of the present application and is not intended to be anexclusive or exhaustive treatment of the present subject matter. Furtherdetails about the present subject matter are found in the detaileddescription and appended claims. The scope of the present invention isdefined by the appended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments are illustrated by way of example in the figures ofthe accompanying drawings. Such embodiments are demonstrative and arenot intended to be exhaustive or exclusive embodiments of the presentsubject matter.

FIG. 1 illustrates generally an example that can include an ambulatorymedical device and an external module.

FIG. 2 illustrates generally an example that can include a processorcircuit, an energy delivery circuit, or a detector circuit.

FIG. 3 illustrates generally an example of an ECG waveform with acorresponding cervical impedance waveform, a corresponding pulsatilesignal waveform, and a neural modulation therapy scheme.

FIG. 4 illustrates generally an example of an ECG waveform with acorresponding cervical impedance waveform, a corresponding pulsatilesignal waveform, and a neural modulation therapy scheme.

FIG. 5 illustrates generally an example that can include a neuralstimulation therapy pulse.

FIG. 6 illustrates generally an example that can include a neuralstimulation therapy pulse that includes an impedance plethysmographysignal component.

FIG. 7A illustrates generally an example that can include a unipolarenergy delivery or sensing system.

FIG. 7B illustrates generally an example that can include a bipolarenergy delivery or sensing system.

FIG. 8 illustrates generally an example that can include providing anelectrical neural modulation therapy.

FIG. 9 illustrates generally an example that can include adjusting aneural modulation therapy parameter.

FIG. 10 illustrates generally an example that can include usinginformation about cardiac activity and providing an electrical neuralmodulation therapy.

FIG. 11 illustrates generally an example that can include trendingpulsatile information.

FIG. 12 illustrates generally an example that can include trendingpulsatile information.

FIG. 13 illustrates generally an example that can include trendingpulsatile information.

DETAILED DESCRIPTION

The following detailed description of the present subject matter refersto the accompanying drawings which show, by way of illustration,specific aspects and examples in which the present subject matter may bepracticed. The examples are described in sufficient detail to enablethose skilled in the art to practice the present subject matter. Otherexamples may be utilized, and structural, logical, and electricalchanges may be made without departing from the scope of the presentsubject matter. References to “an”, “one”, or “various” examples in thisdisclosure are not necessarily to the same example, and such referencescontemplate more than one example. The following detailed descriptionis, therefore, not to be taken in a limiting sense, and the scope isdefined only by the appended claims, along with the full scope of legalequivalents to which such claims are entitled.

The autonomic nervous system (ANS) regulates “involuntary” organs (incontrast to the somatic nervous system, responsible for volitional bodysystem control, e.g., the contraction of skeletal muscles. Examples ofinvoluntary organs can include respiratory and digestive organs, and canalso include blood vessels and the heart. Often, the ANS functions in aninvoluntary, reflexive manner to regulate glands, to regulate muscles inthe skin, eye, stomach, intestines or bladder, or to regulate cardiacmuscle and the muscle cells around blood vessels, for example.

The ANS includes the system pathetic nervous system and theparasympathetic nervous system. The sympathetic nervous system isaffiliated with stress and a “fight or flight response.” Among othereffects, the “fight or flight response” can increase blood pressure andheart rate, such as to increase skeletal muscle blood flow, and candecrease digestion to provide energy for “fighting or fleeing.” Theparasympathetic nervous system is affiliated with relaxation and a “restand digest response” which, among other effects, decreases bloodpressure and heart rate, and increases digestion to conserve energy. Ina healthy person, the ANS maintains normal internal bodily functions andworks in concert with the somatic nervous system.

Electrical neural stimulation therapy can be provided to stimulate thesympathetic or parasympathetic nervous systems, such as to treat avariety disorders. Neural stimulation therapy can be provided incoordination with a patient's physiological cycle to mimic or enhance apatient's natural response to physiological changes. In an example, aphysiological cycle can be identified using fluctuations in measuredcervical impedance over time. In some examples, patient pulsatileinformation can be determined using a measured impedance, such aspulsatile information about a cervical blood vessel (e.g., a carotidartery). Characteristics or features of the cervical impedance orpulsatile information can be used to identify portions of a patient'sphysiological cycle and to time delivery of neural stimulation therapiesin coordination with the physiological cycle. For example, a pulsatilesignal waveform can be generated using the pulsatile information, andneural stimulation therapy can be provided in coordination with anidentified peak of the pulsatile signal waveform.

Stimulating the sympathetic and parasympathetic nervous systems can havephysiological effects manifested many ways. Heart rate or cardiaccontractility can increase in response to sympathetic nervous systemstimulation, or can decrease in response to inhibition of thesympathetic nervous system (or in response to stimulation of theparasympathetic nervous system). For example, depending upon the site ofstimulation, stimulating the sympathetic nervous system can dilate apupil, reduce saliva and mucus production, relax the bronchial muscle,reduce successive waves of involuntary contraction (peristalsis) of thestomach and the motility of the stomach, increase conversion of glycogento glucose by the liver, decrease urine secretion by the kidneys, orconstrict the sphincter of the bladder. Stimulating the parasympatheticnervous system (inhibiting the sympathetic nervous system) constrictsthe pupil, increases saliva and mucus production, contracts thebronchial muscle, increases secretions and motility in the stomach andlarge intestine, increases digestion in the small intestine, increasesurine secretion, and contracts the wall and relaxes the sphincter of thebladder. The functions associated with the sympathetic andparasympathetic nervous systems are many and can be complexly integratedwith each other.

Neural stimulation may be used to treat a variety of cardiovasculardisorders, including heart failure, post-MI remodeling, or hypertension.These conditions are briefly described below.

Heart failure refers to a clinical syndrome in which cardiac functioncauses a below normal cardiac output that can fall below a leveladequate to meet the metabolic demand of peripheral tissues. HF maypresent itself as congestive heart failure (CHF) due to the accompanyingvenous and pulmonary congestion. HF can be due to a variety ofetiologies such as ischemic heart disease. HF patients have impairedautonomic balance, which is associated with LV dysfunction and increasedmortality.

Hypertension is a cause of heart disease and other related cardiacco-morbidities. Hypertension occurs when blood vessels constrict. As aresult, the heart works harder to maintain flow at a higher bloodpressure, which can contribute to HF. Hypertension generally relates tohigh blood pressure, such as a transitory or sustained elevation ofsystemic arterial blood pressure to a level that is likely to inducecardiovascular damage or other adverse consequences. Hypertension hasbeen defined as a systolic blood pressure above 140 mm Hg or a diastolicblood pressure above 90 mm Hg. Consequences of uncontrolled hypertensioninclude, but are not limited to, retinal vascular disease and stroke,left ventricular hypertrophy and failure, myocardial infarction,dissecting aneurysm, and renovascular disease. A large segment of thegeneral population, as well as a large segment of patients implantedwith pacemakers or defibrillators, suffer from hypertension. The longterm mortality as well as the quality of life can be improved for thispopulation if blood pressure and hypertension can be reduced. Manypatients who suffer from hypertension do not respond to treatment, suchas treatments related to lifestyle changes and hypertension drugs.

Cardiac remodeling refers to a complex remodeling process of theventricles that involves structural, biochemical, neurohormonal, andelectrophysiologic factors, which can result following a myocardialinfarction (MI) or other cause of decreased cardiac output. Ventricularremodeling is triggered by a physiological compensatory mechanism thatacts to increase cardiac output due to so-called backward failure whichincreases the diastolic filling pressure of the ventricles and therebyincreases the so-called preload (i.e., the degree to which theventricles are stretched by the volume of blood in the ventricles at theend of diastole). An increase in preload causes an increase in strokevolume during systole, a phenomena known as the Frank-Starlingprinciple. When the ventricles are stretched due to the increasedpreload over a period of time, however, the ventricles become dilated.The enlargement of the ventricular volume causes increased ventricularwall stress at a given systolic pressure. Along with the increasedpressure-volume work done by the ventricle, this acts as a stimulus forhypertrophy of the ventricular myocardium. The disadvantage ofdilatation is the extra workload imposed on normal, residual myocardiumand the increase in wall tension (Laplace's Law) which represent thestimulus for hypertrophy. If hypertrophy is not adequate to matchincreased tension, a vicious cycle ensues which causes further andprogressive dilatation. As the heart begins to dilate, afferentbaroreceptor and cardiopulmonary receptor signals are sent to thevasomotor central nervous system control center, which responds withhormonal secretion and sympathetic discharge. The combination ofhemodynamic, sympathetic nervous system and hormonal alterations (suchas presence or absence of angiotensin converting enzyme (ACE) activity)account for the deleterious alterations in cell structure involved inventricular remodeling. The sustained stresses causing hypertrophyinduce apoptosis (i.e., programmed cell death) of cardiac muscle cellsand eventual wall thinning which causes further deterioration in cardiacfunction. Thus, although ventricular dilation and hypertrophy may atfirst be compensatory and increase cardiac output, the processesultimately result in both systolic and diastolic dysfunction. It hasbeen shown that the extent of ventricular remodeling is positivelycorrelated with increased mortality in post-MI and heart failurepatients.

Implantable or ambulatory medical devices or systems can interact withnerve tissue in a subject body. FIG. 1 illustrates generally an exampleof a system 100, including an implantable medical device (IMD) 105 thatcan be placed subcutaneously or submuscularly in a subject body 101, andcan be configured to interact with nerve tissue in the subject body 101.For example, the IMD) 105 can be configured to use patient physiologicalinformation, such as patient pulsatile information or other patientactivity information, to time delivery of an electrical neuralmodulation therapy using the sensed patient information.

The IMD 105 can include a conductive housing 107 or a processor circuit110, such as can be operably connected to one or more stimulating orsensing circuits. The IMD 105 may be configured to operate autonomouslywith all circuitry residing within the IMD 105, and/or may be configuredto operate with one or more other devices (e.g., IMD(s) and/or externaldevice(s) such as a programmer or an analyzer circuit). For example, theIMD 105 may be configured to deliver neural stimulation therapy and tocommunicate with a cardiac rhythm management (CRM) device, such as apacemaker or defibrillator, which is configured to sense physiologicalparameter(s) or response(s) and provide cardiac rhythm managementtherapy. The IMD 105 can use these sensed physiological parameter(s) orresponse(s) to control the neural stimulation or to provide diagnosticinformation for the patient condition and the efficacy of the neuralstimulation. In an example, a CRM device can use information from theIMD 105, such as information about a neural modulation therapy (e.g.,information about a timing of a neural modulation therapy) to controlthe cardiac rhythm management functions of the CRM device. In someexamples, the IMD 105 can be equipped to provide both neural stimulationand CRM therapies. Combined cardiac and neuromodulation devices arefurther described in Amurthur et al., U.S. Pat. No. 7,664,548, entitledDISTRIBUTED NEUROMODULATION SYSTEM FOR TREATMENT OF CARDIOVASCULARDISEASE, Libbus et al., U.S. Pat. No. 7,647,114, entitled BAROREFLEXMODULATION BASED ON MONITORED CARDIOVASCULAR PARAMETER, and in Libbus etal., U.S. Pat. No. 8,005,543, entitled HEART FAILURE MANAGEMENT SYSTEM,which are incorporated herein by reference in their entirety.

In an example, the IMD 105 can include a communication circuit andantenna, or telemetry coil, such as can be used to communicatewirelessly with an external module 115 or other device. The system 100can include one or more leadless ECG electrodes 109 or other electrodes,such as can be disposed on the housing of the IMD 105. These electrodescan be used to detect heart rate or cardiac arrhythmias, among othercharacteristics of a cardiac cycle.

The external module 115 can include a remote medical device programmeror one or more other remote external modules (e.g., outside of wirelesscommunication range of the IMD 105 antenna, but coupled to the IMD 105using an external device, such as a repeater or network access point).The external module 115 can include a processor circuit configured toprocess information that can be sent to or received from the IMD 105.The information can include medical device programming information,subject data, device data, instructions, alerts, or other information.In an example, the external module 115 can be configured to displayinformation (e.g., information received from the IMD 105) to a user.Further, the local programmer or the remote programmer can be configuredto communicate the sent or received information to a user or physician,such as by sending an alert (e.g., via e-mail) of the status of thesubject 101 or the system 100.

In an example, such as shown in FIG. 1, the IMD 105 can be coupled to animplantable lead system 108. The implantable lead system 108 can includeat least one neural stimulation lead that can be subcutaneouslyimplanted to position electrode(s) to stimulate a neural target in acervical region (e.g., a region at or near the neck) in the subject body101. Examples of cervical neural targets include a vagus nerve, acarotid sinus nerve, a hypoglossal nerve, a glossopharyngeal nerve, aphrenic nerve, baroreceptors and the nerves that innervate and areproximate to the baroreceptors, and chemoreceptors and the nerves thatinnervate and are proximate to the chemoreceptors. The neural target maybe on the left side (e.g. left vagus nerve), or the right side (e.g.right vagus nerve). Additionally, bilateral neural targets may bestimulated. Other neural stimulation lead(s) can include electrodesconfigured to stimulate neural targets outside of a cervical region. Forexample, an electrode can be configured to stimulate a vagus nerve nearthe stomach.

Implanted electrode(s) disposed proximal to or in contact with a neuraltarget can be used to provide neural electrostimulation. A firstelectrode 111, such as a first nerve cuff electrode, can be disposed atthe end of the neural stimulation lead. In an example, the firstelectrode 111 can include a nerve cuff electrode that can be sized,shaped, or otherwise configured to be disposed around a vagus nerve 103.One or more additional nerve cuff electrodes, such as a second electrode112, can be similarly provided. In an example, neural stimulation may beprovided using the first and second electrodes 111 and 112 in a bipolarconfiguration.

Some other vagus nerve stimulation examples can include one or moreelectrodes that can be sized, shaped, or otherwise configured to be fedinto a vessel near the vagus nerve 103, such as for using electrodespositioned within the vessel to intravascularly stimulate the neuraltarget. For example, a neural target can be stimulated using at leastone electrode positioned internally within a jugular vein 102 or acarotid artery 104. The neural stimulation may be bipolar stimulation orunipolar stimulation, such as where the conductive housing 107 of theIMD 105 functions as an electrode.

As discussed above, an implantable electrode can be configured todeliver an electrical neural modulation therapy to one or more of ahypoglossal nerve, a glossopharyngeal nerve, a carotid sinus nerve, orvagus nerve in the cervical region. In an example, an electrical neuralmodulation therapy can additionally or alternatively be delivered toother sympathetic or parasympathetic neural targets, includingperipheral neural targets or spinal neural targets. In an example,electrical neural modulation therapy can be delivered to one or morespinal nerves, such as including in the cervical, thoracic, lumbar, orsacral spinal cord regions. In an example, an electrical neuralmodulation therapy can additionally or alternatively be delivered tobaroreceptor targets, such as to baroreceptor targets in a carotid sinusor pulmonary artery, among other locations. In some examples, anelectrical neural modulation therapy can alternatively or additionallybe delivered to chemoreceptor targets. One or more other neural targets,such as including cardiac nerves or cardiac fat pads can additionally oralternatively be stimulated. For example, electrodes configured todeliver a kidney therapy can be disposed at or near a renal nerve and arenal artery. In an example, some electrodes configured to deliver abladder therapy can be disposed at or near a sacral nerve and a sacralartery.

Other examples can include delivering electrical neural stimulation fromwithin the trachea, or within a blood vessel in close proximity to anerve, such as within the internal jugular vein, the superior vena cava,or the azygous, brachiocephalic, or the subclavian veins. Electricalneural stimulation may be delivered using electrode(s) positioned withina lymphatic vessel. In some cases, a neural target can be stimulatedusing ultrasound or light energy. In an example, the system 100 caninclude one or more satellite electrodes that can be positioned tostimulate a neural target. The satellite electrodes can be coupled tothe IMD 105 using a wireless link, such as to provide a stimulation orcommunication signal.

FIG. 2 illustrates generally an example of a system 200 that cancomprise a portion of the system 100, such as including the IMD 105 andone or more electrode leads. The system 200 can be used to receive andinterpret patient physiological information, such as including cervicalimpedance information, and time delivery of a neural stimulation ormodulation therapy using the patient physiological information.

In the example of FIG. 2, the processor circuit 110 can include multipledata inputs or outputs 231, 232, or 233. Other data inputs or outputs ofthe processor circuit 110 can be coupled to one or more of aphysiological sensor 204, a posture detector circuit 205, a detectorcircuit 222, or an electrical energy delivery circuit 220, or anothercircuit or device. In an example, the data input/output 231 can beconfigured to receive a signal representative of electrical activity ofthe heart of the subject 101. For example, the input/output 231 can beconfigured for use with a device capable of measuring an ECG or otherpatient electrical activity.

The physiological sensor 204 can include a posture sensor, a heart ratesensor, a respiration rate sensor, a respiratory phase sensor, a patientphysical activity level sensor, an accelerometer, or a cardiacarrhythmia sensor, or another type of sensor. The sensor can beconfigured to provide, to the processor circuit 110, a signal indicativeof a patient physiological parameter, or indicative of a change in apatient physiological parameter.

The electrical energy delivery circuit 220 can comprise a pulsegenerator that can be coupled to one or more electrodes (e.g., the firstor second electrodes 111 or 112, or the conductive housing 107), such asincluding an implantable cuff electrode disposed around a neural target.The electrical energy delivery circuit 220 can be configured to generatea current pulse or provide a current pulse to the one or moreelectrodes, such as in response to a control signal provided by theprocessor circuit 110. For example, under control of the processorcircuit 110, the electrical energy delivery circuit 220 can generate andprovide a current pulse to the first electrode 111, such as in responseto a trigger signal received from the physiological sensor 204. In anexample, the processor circuit 110 can be configured use informationabout a patient physiological cycle, such as pulsatile informationderived from a patient cervical impedance signal, to initiate or adjusta neural modulation therapy, such as an electrical neural modulationtherapy that can be provided using the electrical energy deliverycircuit 220.

In an example, the detector circuit 222 can be configured to receiveelectrical signals from one or more electrodes, such as the first orsecond electrodes 111 or 112, or the conductive housing 107. In anexample, the detector circuit 222 can be configured to receive ormeasure at least one of a current, voltage, or impedance signal in or onthe subject body 101. The measured current, voltage, or impedance signalreceived by the detector circuit 222 can be received by the processorcircuit 110 for further processing. In an example, the received ormeasured information can be passed from the processor circuit 110 to adifferent, second processor circuit, such as using the data input/output231. For example, the received or measured information can betransferred to the external module 115 for further analysis, processing,or for display to a patient or physician. In an example, the detectorcircuit 222 can be used to detect one or more physiological parametersor responses, such as including blood pressure, cardiac activityparameters such as heart rate, and respiration parameters such as tidalvolume or minute ventilation.

In an example, the electrical energy delivery circuit 220 can beconfigured to use a constant current source to deliver a current signalbetween two or more electrodes, such as can be disposed in a cervical,thoracic, or other body region, proximal to a nerve. The detectorcircuit 222 can be configured to detect a responsive voltage signalusing the same or different electrodes. Fluctuations in the responsivevoltage signal can be analyzed (e.g., using plethysmography techniques),such as to determine pulsatile information indicative of a change in ablood vessel dimension.

FIG. 3 illustrates generally several corresponding waveforms indicativeof physiological patient activity, such as including an ECG waveform301, a corresponding pulsatile signal waveform 330, or a correspondingcervical impedance waveform 340. In an example, a blood vessel impedancesignal can be included. One or several of the corresponding waveformscan be measured using various systems or devices, such as using thesystem 200. The several waveforms can be illustrated using a commonorigin and time axis, as shown. FIG. 3 further illustrates an adjustableneural modulation therapy scheme 350, such as can correspond to one ormore indications of physiological patient activity.

In an example, such as shown in FIG. 3, an ECG waveform 301 can beobtained, such as using at least two leadless ECG electrodes disposed onthe housing of the IMD 105. In an example, the ECG waveform 301 can beobtained using a device other than the 1 MD 105, such as using anexternal monitoring device.

In an example, such as shown in FIG. 3, a cervical impedance waveform340 can be obtained, such as using one or more electrodes disposed in apatient's cervical region. For example, the cervical impedance waveform340 can be obtained using a bipolar electrode configuration, such asusing the first and second electrodes 111 and 112 illustrated in thesystem 100, among other configurations. In an example, fluctuations inthe cervical impedance waveform 340 can be correlated to cardiacactivity. The fluctuations can be used to determine a patient heart rateor a patient heart rate signal. In an example, fluctuations in thecervical impedance waveform 340 can be correlated to fluctuations in ablood vessel dimension, such as can be used to obtain a blood vesselexpansion signal or pulsatile signal.

The pulsatile signal waveform 330 can be measured using, among othertechniques, sonomicrometry or impedance plethysmography. For example,the pulsatile signal waveform 330 can be derived using plethysmographyanalysis techniques and cervical impedance information, such as usingthe cervical impedance waveform 340. In an example, a physiologicalblood pressure sensor (e.g., the physiological sensor 204) can bedisposed in or near the carotid artery 104, such as can be used toprovide pulse pressure information to determine pulsatile information(e.g., including the pulsatile signal waveform 330). The pulsatilesignal waveform 330 can indicate, among other things, a relative changein a diameter or portion of a diameter of a blood vessel, such as overone or more cardiac cycles.

Various physiological parameters can be used to determine or providepulsatile information, such as can be used to form the pulsatile signalwaveform 330. For example, pulsatile information can include informationabout one or more of a patient blood pressure, pulse pressure, relativepulse pressure, phase of a blood pressure cycle, or heart sounds. Otherparameters or information can be derived using pulsatile information(e.g., using the pulsatile signal waveform 330), such as including heartrate, pulse transit time, or arterial compliance information.

In the example of FIG. 3, changes in blood vessel impedance, thoracicimpedance, or cervical impedance can correspond with changes in a bloodvessel dimension. For example, information obtained from a blood vesselimpedance signal (not shown in FIG. 3) can be used to derive dimensionalinformation about a blood vessel, such as including information about apresence or passage of a blood pressure pulse. In an example, a relativemaximum blood vessel impedance, such as corresponding to a first cardiaccycle, can precede a corresponding relative maximum 331 of the pulsatilesignal waveform 330, such as by a time Δt. Subsequent relative maximumand minimum impedances can similarly correspond to respective relativemaxima and minima of the pulsatile signal waveform 330 such that theblood vessel impedance signal can be an effective surrogate indicationof pulsatile fluctuations (e.g., pulse pressure fluctuations), or viceversa.

Information about a patient physiological status can be discerned usingone or more of the waveforms illustrated in FIG. 3. In an example,relationships between or among waveform characteristics can provideinformation about a patient health status. For example, informationabout a pulsatile signal amplitude or about timing of adjacent peaks ofthe pulsatile signal waveform 330 can provide information about apatient health status. For example, a relative maximum of the ECG signal301 (e.g., a peak of an R-wave) and a relative maximum of the pulsatilesignal waveform 330 can be offset by a time of about Δt₁. In an exampleΔt₁ can be used to provide information about a patient physiologicalstatus or to trigger a patient therapy, such as in response to alengthening interval Δt₁. In an example, lengthening Δt₁ can indicate aworsening dissynchrony between cardiac electrical activity and a patientpulse pressure.

In an example, information about a patient physiological status or apatient physiological activity can be used to coordinate delivery of aneural modulation therapy. For example, one or more patientphysiological events, patient physiological cycle characteristics, orother indications of patient physiological activity can be used tocoordinate delivery of a neural modulation therapy. Patientphysiological activity can be identified using one or more of thepulsatile signal waveform 330, the cervical impedance waveform 340, theECG waveform 301, or some other indication of a patient physiologicalactivity. In an example, a waveform characteristic can be used toidentify a patient physiological event or to identify a portion of apatient physiological cycle, such as can trigger a neural modulationtherapy. In an example, one or more neural modulation therapy parameterscan be adjusted in response to an identified patient physiologicalactivity. A neural modulation therapy parameter can be used to define ordetermine one or more neural modulation therapy characteristics, such asa neural modulation therapy pulse characteristic (e.g., amplitude,duration, etc.).

In an example, the pulsatile signal waveform 330 or the cervicalimpedance waveform 340 can be used to determine several physiologicalevents or cycle characteristics, such as including blood pressure, pulsepressure, pulse transit time (PTT), or relative pulse pressure (RPP),among others. Such indications of physiological activity can be used toprovide information about a patient physiological status, such asinformation about heart rate, arterial compliance or stiffness, cardiaccontractility, autonomic status, pulmonary vein distension, respiratoryeffort or disturbance (e.g., including apnea), blood pressure cyclephase, or a patient fluid status, among other things. Such informationcan be used to monitor a health patient status, to provide informationfor patient diagnostics, or to titrate a patient therapy, such asincluding an electrical neural modulation therapy.

In an example, such as shown in FIG. 3, a pulse transit time (PTT) canbe determined. The pulse transit time can be a time interval between atriggering event and a pulse receipt event (e.g., a blood pressure pulsereceipt event) in a blood vessel. In an example, a portion of the ECGsignal 301 can be used as a reference to provide a PTT triggering event.The PTT triggering event can include a cardiac event, such ascorresponding to a particular portion of a QRS complex. For example, apulse transit time can be the time for an arterial pulse pressure waveto travel from a left ventricle of a heart to a peripheral body site,such as to the carotid artery. In some examples, a PTT triggering eventcan include the occurrence of a heart sound, or a receipt of a pulse ina first location in a blood vessel, or an emptying of the leftventricle.

In an example, such as shown in FIG. 3, a PTT triggering event can occurat a time t₁, or at a time when the QRS cormplex of a particular cardiaccycle exhibits a minimum amplitude. In an example, a PTT pulse receiptevent can occur when a pulse or pressure wave arrives at or passesthrough a particular blood vessel location. For example, the pulsereceipt event can include, among other things, a maximum arterialpressure, a threshold change in a vessel dimension, or a thresholdchange in a received impedance signal. In an example, such as shown inFIG. 3, a pulse receipt event can correspond to an inflection point 341of the cervical impedance waveform 340, such as can occur at a time t₂.In this example, a pulse transit time can be represented by an intervalΔt₂, or by an interval between t₁ and t₂. Pulse transit time, andparticularly changes in pulse transit time, can be correlated with oneor more physiological changes or changes in patient health status. Thus,monitoring pulse transit time can provide diagnostic information about apatient or can indicate a patient therapy, such as a neural modulationtherapy.

Relative pulse pressure can be a useful parameter that can bedetermined, such as using impedance plethysmography analysis techniqueswith impedance signals obtained in a cervical region of the subject body101. A relative pulse pressure can be conceptualized as a differencebetween systolic and diastolic pressures, such as relative to priormeasured pressure values. In an example, such as shown in FIG. 3, afirst relative pulse pressure Δp₁ can be measured using information fromthe cervical impedance waveform 340 as a surrogate for vessel pressure.Maxima and minima of the cervical impedance waveform 340 can correspondto maxima and minima of a vessel pressure, such as corresponding tomaximum systolic and minimum diastolic pressures. A second relativepulse pressure Δp₂ can be measured at a subsequent time. In an example,a change in relative pulse pressure from Δp₁) and Δp₂ (e.g., adifference between a first measured relative pulse pressure and a secondmeasured relative pulse pressure) can indicate a change in a patienthealth status. In an example, information about a relative pulsepressure can be similarly determined using the pulsatile signal waveform330.

In an example, information about a pulse transit time or a relativepulse pressure can be used to initiate or adjust a neural modulationtherapy. For example, a neural modulation therapy can be provided when apulse transit time exceeds or falls below a predetermined thresholdpulse transit time, or a neural modulation therapy can be provided whena relative pulse pressure exceeds or falls below a predeterminedthreshold relative pulse pressure. In an example, a combination ofinformation about a pulse transit time or a relative pulse pressure canbe used to initiate or adjust a neural modulation therapy.

In an example, a neural modulation therapy can be provided according toa first neural modulation therapy scheme 350, such as using one or moreneural modulation therapy parameters to determine the characteristics ofthe neural modulation therapy. For example, a neural modulation therapycan be provided in coordination with a patient physiological event orpatient physiological cycle. In an example, a neural modulation therapycan be provided in response to an identified pulse transit time,relative pulse pressure, or other identified physiological statusindication.

In an example, a neural modulation therapy can be provided according tothe first neural modulation therapy scheme 350, such as can be definedby one or more neural modulation signal characteristics. The neuralmodulation therapy can be provided to a neural target, such ascontinuously for a particular therapy delivery duration Δt_(n). In anexample, a discrete number of electrical neural modulation therapysignals or pulses can be provided to a neural target. In the example ofFIG. 3, for example, a burst of six discrete electrical neuralmodulation therapy pulses can be provided, such as with an interveningdelay between each pulse delivery. In an example, electrical neuralmodulation therapy pulses can be provided, such as after a first delayΔt_(D1) from an identified physiological fiducial, such as correspondingto an identified patient physiological event (e.g., a pulsatile signalwaveform peak event) or patient physiological cycle (e.g., a pulsatilesignal waveform cycle).

In an example, a number, or quantity, of neural modulation therapypulses can be adjusted, such as according to a neural modulation therapyparameter. For example, FIG. 4 illustrates generally a second neuralmodulation therapy scheme 352, such as comprising a burst of fourdiscrete electrical neural modulation therapy pulses, such as with anintervening delay between each pulse delivery (e.g., the interveningdelay can be the same or different than the intervening delay in theexample of the first neural modulation therapy scheme 350). The numberof discrete electrical neural modulation therapy pulses in the neuralmodulation therapy scheme can be adjusted to be zero or more, such asaccording to a neural modulation therapy parameter.

In an example, a delay preceding a neural modulation therapy deliveryscheme can be adjusted, such as according to a neural modulation therapyparameter. FIG. 4 illustrates generally a second delay, Δt_(D2), such asextending from an identified physiological fiducial (e.g., at t₃ or t₄)to an initial delivery of a neural modulation therapy pulse. The delaycan be adjusted to be zero or more, such as according to a neuralmodulation therapy parameter.

Referring to FIG. 3 or FIG. 4, an amplitude of a portion of thepulsatile signal waveform 330 can be used to adjust a neural modulationtherapy parameter or initiate a neural modulation therapy. For example,a peak amplitude 331 of the pulsatile signal waveform 330, such as anabsolute peak during a particular time window, or a relative peak, suchas relative to one or more of a predetermined threshold, apreviously-observed minimum, or a previously-observed maximum of thepulsatile signal waveform 330, can be used to indicate a neuralmodulation therapy. That is, upon detection of a peak of the pulsatilesignal waveform 330, such as by the processor circuit 110, a neuralmodulation therapy parameter can optionally be determined, or anelectrical neural modulation therapy (e.g., comprising one or moreneural modulation therapy pulses) can be provided to a neural target(e.g., a cervical neural target) using the electrical energy deliverycircuit 220 and the neural modulation therapy parameter.

In an example, an electrical neural modulation therapy can be provided,such as in continuous burst fashion, while an amplitude of a portion ofthe pulsatile signal waveform 330 exceeds a predetermined thresholdamplitude. For example, the electrical neural modulation therapy can beinitiated in response to a first identified characteristic of thepulsatile signal waveform 330 (e.g., as the waveform exceeds apredetermined threshold amplitude), and the electrical neural modulationtherapy can be terminated in response to a second, subsequentlyidentified characteristic of the pulsatile signal waveform 330 (e.g., asthe waveform falls below the predetermined threshold amplitude).

In an example, a timing characteristic of a portion of the pulsatilesignal waveform 330 can be used to initiate or adjust a neuralmodulation therapy. For example, a timing of a portion of the pulsatilesignal waveform 330 can include a time indicative of a particularcharacteristic of the pulsatile signal waveform 330, such as a timeindicative of a pulsatile signal waveform peak, a pulsatile signalwaveform inflection point, a pulsatile signal waveform minimum, or atime indicative of some other characteristic of the pulsatile signalwaveform. A timing characteristic of a portion of the pulsatile signalwaveform 330 can include a duration, such as corresponding to aninterval between an identified first characteristic of the pulsatilesignal waveform 330 (e.g., an identified peak, inflection point,relative minimum or maximum, etc.) and some other, subsequentlyidentified waveform characteristic or event, such as corresponding tothe pulsatile signal waveform 330 or another waveform. For example, atiming of a portion of the pulsatile signal waveform 330 can include aninterval between an identified relative peak of the pulsatile signalwaveform 330 and a characteristic of the ECG waveform 601, such as anR-wave peak (e.g., the interval Δt₁ illustrated in FIG. 3). The intervalcan be compared to a threshold interval and, when the duration exceedsor falls below a particular threshold duration, a neural modulationtherapy can be initiated, such as according to the neural modulationtherapy scheme 350, such as using the processor circuit 110. In anexample, a timing of a portion of the pulsatile signal waveform 330 caninclude an interval between identified peaks of the pulsatile signalwaveform 330, such as corresponding to adjacent cardiac cycles (e.g.,the interval Δt₃ illustrated in FIG. 3).

In an example, a timing of a portion of the pulsatile signal waveform330 can include an interval between a pulsatile signal waveform 330threshold crossing (e.g., in the example of FIG. 4, a point at which thepulsatile signal waveform 330 crosses a pulsatile signal threshold 332)and a pulsatile signal waveform 330 relative maximum. In an example, theinterval can be compared to a threshold interval, such as to indicate aneural modulation therapy, or to adjust a neural modulation therapyparameter. Other timings of the pulsatile signal waveform 330, such asin coordination with one or more of the cervical impedance waveform 340,the ECG waveform 301, or other indications of physiological patientactivity, can be used.

In an example, a frequency of a portion of the pulsatile signal waveform330 can be used to adjust a neural modulation therapy parameter orinitiate a neural modulation therapy. For example, changes in afrequency of the pulsatile signal waveform 330, such as can bedetermined using the processor circuit 110, can be used to suppress orindicate a neural modulation therapy. In an example, a frequency changecan indicate an adjustment of a neural modulation therapy parameter.

In an example, an increasing frequency of the pulsatile signal waveform330 can indicate an increasing patient heart rate. In response to theincreased frequency, a neural modulation therapy parameter can beadjusted, such as corresponding to one or more neural modulation therapypulse characteristics, such as an increased pulse amplitude or increasedpulse delivery frequency. In an example, a frequency of othercharacteristics of the pulsatile signal waveform 330 can be monitored ortrended, such as to provide information about a patient health status ortrend. For example, a frequency of threshold amplitude crossings of thepulsatile signal waveform 330 can be monitored or trended.

In an example, a shape of a portion of the pulsatile signal waveform 330can be used to adjust a neural modulation therapy parameter or initiatea neural modulation therapy. For example, a slope of a portion of thepulsatile signal waveform 330 can be used. In an example, a decreasingslope, such as decreasing at a particular rate, can correspond to afirst neural modulation therapy parameter, and an increasing slope, suchas increasing at a particular rate, can correspond to a different secondneural modulation therapy parameter. Other indications of shape of thepulsatile signal waveform 330 can be used. For example, width of apulsatile signal waveform peak can be assessed, such as by the processorcircuit 110, to adjust or initiate a neural modulation therapy.

In an example, an integral of a portion of the pulsatile signal waveform330 can be used to adjust a neural modulation therapy parameter orinitiate a neural modulation therapy. For example, an integral of aportion of the pulsatile signal waveform 330 can be used as anindication of a shape of the pulsatile signal waveform 330, such as canprovide information about an area below or above a portion of thepulsatile signal waveform 330 curve. The area information can be used,such as by the processor circuit 110, to adjust or initiate a neuralmodulation therapy. Similarly, a derivative of a portion of thepulsatile signal waveform 330 can be used to initiate or adjust a neuralmodulation therapy.

In an example, a sum, difference, linear combination, ratio, or productof characteristics, such as of the pulsatile signal waveform 330described above, among other characteristics of the various waveforms orother features indicative of patient physiological activity, can be usedto adjust a neural modulation therapy parameter or initiate a neuralmodulation therapy. For example, information about a difference or sumof adjacent peak magnitudes of the pulsatile signal waveform 330 can beused to adjust or initiate a neural modulation therapy.

In an example where the IMD 105 includes a CRM component or iscommunicatively coupled to a CRM device, information from any one ormore of the ECG waveform 301, the pulsatile signal waveform 330, or thecervical impedance waveform 340 can be used to initiate or adjust a CRMtherapy. For example, any of the characteristics of the pulsatile signalwaveform 330 or the cervical impedance waveform 340, among others, canbe used to trigger CRMvI or neural modulation therapies, or both. In anexample, a characteristic of the cervical impedance waveform 340 (e.g.,a frequency characteristic of the cervical impedance waveform 340) canbe used to initiate or adjust a bradycardia or anti-tachycardia therapy.

A neural modulation therapy can be provided to a neural target using anelectrical neural modulation therapy signal. An electrical neuralmodulation therapy signal can be defined by multiple signalcharacteristics, including amplitude, frequency, shape, duration, DCoffset, timing, delay, or number of phases, among other characteristics.FIG. 5 illustrates generally an example of a biphasic electrical neuralmodulation therapy signal 501, such as comprising two neural modulationtherapy pulses. In an example, the neural modulation therapy signal 501can be provided to, among other locations, a cervical region of thesubject body 101.

The neural modulation therapy signal 501 can be provided according toone or more neural modulation therapy parameters that can be used todetermine or define one or more characteristics of the neural modulationtherapy signal 501. For example, using a neural modulation therapyparameter, the processor circuit 110 can 301 instruct the electricalenergy delivery circuit 220 to provide a neural modulation therapysignal having particular signal characteristics (e.g., particular signalcharacteristics such as a particular amplitude, duration, or timing,etc.).

In an example, the neural modulation therapy signal 501 can include abiphasic pulse signal having a first, positive phase duration of about300 μs at an amplitude of about 100-4000 μA. The neural modulationtherapy signal 501 can include a second, negative phase, such asfollowing the first phase and having an initial minimum magnitude lessthan zero. The second, negative phase can include a positively slopedportion, extending from the initial minimum, such as continuously orexponentially increasing toward zero.

In an example, the neural modulation therapy signal 501 can be deliveredto the subject body 101 substantially continuously, such as at a pulsefrequency of about 20 Hz. At 510, FIG. 5 illustrates generally agraphical representation of such a continuous delivery of the neuralmodulation therapy signal 501.

In another example, the neural modulation therapy signal 501 can bedelivered to the subject body 101 in burst fashion. For example, theneural stimulation signal can be delivered intermittently, such as bydelivering a train or burst of neural modulation therapy pulses forabout 10 seconds, pausing for about 50 seconds, and resuming deliveringthe signal for a subsequent 10 second burst. During the about 10 secondsthat the neural modulation therapy pulses are applied, the pulses can beapplied at a pulse frequency of about 20 Hz. The intermittent neuralstimulation may be delivered according to a programmed schedule that maybe used to control start times, or stop times, or duration of the pulsetrains, or combinations thereof. Programmed intermittent neuralstimulation therapies may be used to treat chronic conditions such asheart failure and hypertension. At 520, FIG. 5 illustrates generally agraphical representation of such discontinuous, or burst, delivery ofthe neural modulation therapy signal 501.

In an example, a neural modulation therapy pulse can be used to delivera patient therapy and to deliver a test electrical signal to a patientbody, such as an impedance measurement pulse. In an example, some neuralmodulation therapy pulse characteristics can be common to impedancemeasurement pulses (e.g., non-neurostimulating pulses) and neuralmodulation therapy pulses, such as vagus nerve stimulation (VNS) pulses.In an example, both neurostimulating and non-neurostimulating signalscan include at least some similar pulse characteristics, such as similaramplitude, similar pulse width, or similar frequency. This overlap inpulse signal characteristics, such as in combination with an appropriateelectrode location configuration, can enable dual use of the impedancemeasurement and neural stimulation pulses, such as to provide neuralmodulation therapy or to evoke an impedance measurement response signalusing the neural modulation therapy pulse energy as an “excitation” or“test” energy for obtaining the impedance information.

One or several benefits, such as including improved signal to noiseperformance and noise rejection, can be obtained by using neuralmodulation therapy pulses as pulses for impedance measurements. In anexample, a neural modulation therapy pulse can be delivered at arelatively high current level that exceeds a nerve tissue capturethreshold. In contrast, pulses used exclusively for impedancemeasurements can be delivered at relatively low, non-tissue stimulatingcurrent levels. By using a higher-amplitude neural modulation therapypulse as at least a portion of an impedance measurement pulse, afunctional impedance measurement response signal can be more likely tobe received, and concerns about tissue capture during impedancemeasurement can be reduced or eliminated. In addition, using arelatively high amplitude therapy pulse as an impedance measurementpulse can provide better resolution of the responsive or receivedmeasurement signals. For example, a signal to noise ratio of animpedance measurement-only response signal relative to backgroundelectrical noise can be improved. Because of the higher amplitude, therecan be reduced susceptibility to interference, both internally to thesubject body 101 and externally.

In addition, combining therapy pulses and impedance measurement pulsescan improve the longevity of a medical device, such as by reducing powerconsumption requirements by consolidating the number of individualpulses that are delivered to the subject body. In addition, by usingneural stimulation signals as impedance plethysmography pulses, overallsystem design can be facilitated or other trade-offs can advantageouslybe made because there is little or no need to avoid collisions betweenneural stimulation pulses and impedance plethysmography pulses.

FIG. 6 illustrates generally an example that can include a pulse thatincludes neural stimulation and impedance plethysmography components. Apulse waveform 600 can include at least a first composite pulsecomponent 610. The illustrated first composite pulse component 610includes a neural stimulation positive phase pulse component 601, animpedance plethysmography pulse component 602, and a neural stimulationnegative phase pulse component 603. The pulse waveform 600 can include asecond pulse component 604. The illustrated second pulse component 604includes a positive phase 605 and a negative phase 606 of an impedanceplethysmography pulse, such as can be used to evoke an electricalresponse that can be used to measure impedance.

In an example, such as shown in FIG. 6, an impedance plethysmographypulse can be appended to a trailing portion of the neural stimulationpositive phase pulse component 601. This configuration can help improverepeatability of impedance plethysmography measurements at least becausea consistent amplitude for the impedance plethysmography pulse (e.g.,about 320 μA peak) can be used regardless of an amplitude of the neuralstimulation pulse signal.

In an example, one or a series of impedance measurement pulses may bedelivered when neural modulation therapy is not being delivered. Duringthese “off” portions of a neural modulation therapy pulse train,impedance plethysmography pulses (e.g., non-tissue-stimulating pulses)can be provided to the subject body 101 to obtain impedancemeasurements. A responsive impedance signal can be used to identifyphases of a blood pressure cycle (e.g. systole and diastole). The timingof one or both of these phases can be used to control the timing of theneural stimulation therapy. For example, the neural stimulation therapymay be used to elicit a baroreflex response that mimics or augments anatural baroreflex response induced by the baroreceptor response topulsating blood flow.

In an example, dimensional changes of a blood vessel can be correlatedwith changes in a patient pulse pressure. For example, when a pulse orblood surge passes through a vessel, the vessel can expand as thepressure exerted by the blood acts upon the vessel walls. In an example,expansion or contraction of a cervical blood vessel can be determinedusing a cervical impedance signal, such as after a cervical impedancemeasurement response signal is filtered or otherwise processed toidentify the signal components of interest. For example, the processorcircuit 110 can be configured to receive an impedance measurementresponse signal, such as via the detector circuit 222, and can beconfigured to determine impedance measurement response signal componentsrepresentative of a pulse pressure. In an example, a decrease in anamplitude of a cervical impedance signal can indicate a full or expandedcervical blood vessel. In an example, information about a blood vesseldimensional change can be used as a surrogate for information aboutbaroreceptor activity.

In an example, such as shown in FIG. 6 at 604, an impedance measurementpulse can include a biphasic current pulse having a pulse duration ofabout 40 μs and a peak amplitude of about 80 to 320 μA. In an example,the impedance measurement pulse can be delivered to the subject body 101about every 50 ms such that an impedance measurement response signal canbe continuously or recurrently sampled at about 20 Hz. Continuously orrecurrently sampled impedance measurement response signals can be usedto provide impedance response information over time.

Unipolar and bipolar electrode configurations can be used to provide animpedance measurement pulse, to provide electrical neural modulationtherapy, or to receive responsive electrical signals, such as animpedance signal. FIG. 7A illustrates generally an example of unipolarmeasurement and therapy delivery configurations, and FIG. 7B illustratesgenerally bipolar measurement and therapy delivery configurations. Someembodiments use a unipolar measurement configuration and a bipolartherapy delivery configuration, and some embodiments use a unipolartherapy delivery configuration and a bipolar measurement configuration.

The embodiments illustrated generally in FIGS. 7A and 7B can be used toacquire an impedance signal, such as using one or more electrodesdisposed within the body (e.g., using the first and second electrodes111, 112, such as disposed near a vagus nerve 103). Characteristics ofthe impedance signal can be used to control a neural stimulationtherapy. The impedance signal may also be used to manage or monitor atherapy or a condition of the patient, such as heart failure status.

In an example, an acquired impedance signal can be interpreted orprocessed using one or more plethysmography techniques, such as usingthe processor circuit 110 to interpret a relatively small change inelectrical impedance in a body and, in response, provide a neuralmodulation therapy. An impedance signal for plethysmography analysis canbe obtained using one or more electrodes that can be disposed in, amongother locations, a cervical region of the patient body 101, such asusing one or more cuff electrodes that can be disposed at or around thevagus nerve 103. In an example, impedance plethysmography can be used todetermine a change in a blood vessel dimension (e.g., a change in adimension of the carotid artery 104), such as a change in across-sectional area or a radial dimension. In an example, impedanceplethysmography can be used to determine, among other things, pulsatilemotion of a blood vessel, blood flow, or blood pressure.

FIG. 7A illustrates generally an example of a system 201 that can beconfigured to provide a unipolar electrical signal to the subject body101. For example, the processor circuit 110 can initiate an electricalcurrent pulse that can be provided along the current path illustrated inFIG. 7A (e.g., an impedance measurement pulse, such as can be used toevoke an impedance response, or an electrical therapy pulse, such as canbe used to provide a neural modulation therapy). The electrical energydelivery circuit 220 can be configured to deliver the current pulseusing the first electrode 111, such as to deliver the current pulse to aneural stimulation target location proximate to the vagus nerve 103.

In the example of FIG. 7A, the system 201 can be configured to receivean impedance measurement response signal, such as in response to theelectrical current pulse. The impedance measurement response signal canbe received across a cervical or thoracic region of the subject body101. For example, the detector circuit 222 can be configured to measurea thoracic impedance measurement response signal by receiving anelectrical response signal (e.g., using a voltage signal, denoted inFIG. 7A by the voltage measurement circuit V) using the conductivehousing 107 and at least one of the first electrode 111 or the secondelectrode 112, such as when the conductive housing 107 is disposed inthe thorax of the subject 101.

FIG. 71B illustrates generally an example of a system 202 that can beconfigured to provide a bipolar electrical stimulation signal to acervical region in the patient body 101, such as at or near the vagusnerve 103. For example, the bipolar configuration of the system 202 canbe used to provide a focused delivery of electrical energy to a regionin the subject body 101 (e.g., a cervical region). For example, theelectrical energy delivery circuit 220 can be configured to deliver acurrent pulse to a target cervical location using multiple electrodesdisposed at or near the target location, such as using the firstelectrode 111 and the second electrode 112. In the example of FIG. 7B, acurrent path is denoted I.

The system 202 can be configured to receive an impedance measurementresponse signal, such as a voltage signal obtained across a cervicalregion of the subject body 101. For example, the detector circuit 222can be configured to measure a cervical impedance by receiving animpedance measurement response signal using the first electrode 111 andthe second electrode 112, such as when the first and second electrodesare disposed in the cervical region. In the example of FIG. 7B, theelectrical response signal can include a voltage signal detected by thevoltage measurement circuit V, such as including a voltage between thefirst and second electrodes 111 and 112.

In an example, the first electrode 111 and the second electrode 112 canbe electrodes disposed on a single implantable lead, such as amultipolar electrode lead comprising two or more electrodes. Forexample, the first electrode 111 and the second electrode 112 can be twoof four electrodes on a quadripolar electrode lead. In an example, thesame or different electrodes can be used to deliver a current pulse orto receive a corresponding, responsive voltage signal. Illustrativeexamples of electrode configurations for performing impedancemeasurements are described in Stahmann et al., U.S. Pat. No. 7,387,610,entitled THORACIC IMPEDANCE DETECTION WITH BLOOD RESISTIVITYCOMPENSATION, which is incorporated herein by reference in its entirety.

In an example, the processor circuit 110 can execute an electrodeselection algorithm to select appropriate electrodes for deliveringelectrical pulses or receiving electrical response signals. For example,the first electrode 111 or the second electrode 112 can be selected fromamong three or more available electrodes, such as disposed on any one ormore implantable leads in the implantable lead system 108, on the IMD105, or elsewhere. In an example, an electrode selection algorithm cananalyze one or more electrode selection parameters, such as impedancesignal strength or repeatability, such as using available pairs orcombinations of electrodes. The electrode selection parameters can thenbe used to select electrodes for energy delivery or measurement.

FIG. 8 illustrates generally an example that can include providing anelectrical neural modulation therapy. At 810, an electrical test signalcan be provided internally within a patient body, such as using one ormore of the systems 100, 201, or 202, among others. For example, theelectrical test signal can be a non-tissue stimulating (e.g.,sub-capture threshold) signal, such as comprising one or more electricaltest pulses, such as impedance measurement plethysmography pulses. Theelectrical test signal can include a tissue stimulating signal, such asa neural modulation therapy signal, such as configured to provide anautonomic modulation therapy to a patient nerve. In an example, theelectrical test signal can be delivered to a cervical region within asubject body 101, such as at or near the vagus nerve 103 and proximal tothe carotid artery 104.

At 820, a cervical impedance signal can be detected, such as using thedetector circuit 222. In an example, the cervical impedance signal canbe detected or received in response to the electrical test signalprovided at 810. In an example, the cervical impedance signal can beanalyzed as an impedance plethysmography signal, such as using theprocessor circuit 110, or stored using a processor-readable mediumcoupled to the processor circuit 110.

At 860, a pulsatile signal can be determined, such as using the detectedcervical impedance signal. In an example, a cervical impedance signalcan be filtered, analyzed, or otherwise processed to determine apulsatile signal, such as a signal indicative of fluctuations in acarotid artery pulse pressure. In some cases, particular frequencycomponents (e.g., frequency components determined experimentally orcomponents that are unique to a particular patient) can be eliminatedfrom a cervical impedance signal to acquire an accurate pulsatilesignal. As shown generally in FIG. 3, for example, a pulsatile signal(e.g., the pulsatile signal waveform 330) can correspond generally to acervical impedance signal. For example, an inflection pointcharacteristic of the pulsatile signal waveform 330 can temporallycorrespond with an inflection point characteristic of the cervicalimpedance waveform 340, or a variable interval can exist between theinflection point characteristics. In an example, the variable intervalbetween the inflection point characteristics can include usefulinformation about a patient physiological status, such as can be used toinitiate or adjust a neural modulation therapy.

In an example, the pulsatile signal determined at 860 can be a functionof a vessel dimension, such as can be determined using the detectedcervical impedance signal as an impedance plethysmography signal. Usingimpedance plethysmography, a value of a detected impedance change can becorrelated with a change in a blood vessel volume or a change in a bloodvessel dimension. In an example, a vessel dimension can be determined byanalyzing differences in the detected cervical impedance signal,including differences in amplitude, phase, or other features orcharacteristics of the impedance signal. In an example, the determinedvessel dimension can be a radial blood vessel dimension (e.g., a radialdimension of a carotid artery), changes in which can be correlated tochanges in pulse pressure.

At 880, a pulsatile signal characteristic can be identified. As showngenerally in FIGS. 3 and 4, a pulsatile signal (e.g., the pulsatilesignal waveform 330) can include numerous characteristics or features.For example, pulsatile signal characteristics can include, among others,a timing of a portion of the pulsatile signal, an amplitude of thepulsatile signal, a frequency determined using the pulsatile signal, ashape of the pulsatile signal, an integral of the pulsatile signal, aderivative of a portion of the pulsatile signal, or a ratio, sum,difference, linear combination, or product of characteristics of thepulsatile signal or another physiological signal, such as describedabove in the discussion of FIGS. 3 and 4. In an example, a pulsatilesignal characteristic can include a composite characteristic, such asincluding information about one or more characteristics of otherphysiological signals. For example, a pulsatile signal characteristiccan include information about a characteristic of a pulse pressuresignal (e.g., a peak pulse pressure) and information about acharacteristic of a corresponding ECG signal (e.g., an amplitude of theECG signal at the time of the peak pulse pressure, or an intervalbetween an ECG signal characteristic and the peak pulse pressure). In anexample, at 880, an identified pulsatile signal characteristic caninclude a comparison of one or more pulsatile signal characteristicswith a predefined threshold, or a comparison with previously acquired,patient-specific pulsatile signal characteristic information.

In an example, the processor circuit 110 can be configured to determinea reference pulsatile signal characteristic during a device learningperiod. The learning period can include multiple physiological cycles,such as corresponding to one or more patient physical activity levels.In an example, a reference pulsatile signal characteristic can bedetermined using information obtained while a patient is at rest, suchas over multiple cardiac cycles, such as including averaged signalcharacteristic information. The pulsatile characteristic information canbe measured at about the same time during or after a cardiaccontraction, such as for each of the multiple cardiac cycles.

At 890, an electrical neural modulation therapy can be provided. In anexample, the electrical neural modulation therapy can be provided usingthe system 100, 201, or 202, among others, such as using one or moreelectrical neural modulation therapy parameters to define the therapy.In an example, the pulsatile signal characteristic identified at 880 canbe used to provide the electrical neural modulation therapy at 890. Forexample, the pulsatile signal characteristic identified at 880 can beused to time delivery of the electrical neural modulation therapy, suchas by providing a fiducial reference point from which to begin a neuralmodulation therapy scheme (e.g., the first neural modulation therapyscheme 350, among other schemes).

In an example, such as shown in FIG. 8 at 801 or 889, physiologicalstatus information can be received from a physiological sensor (e.g.,the physiological sensor 204). In an example, physiological statusinformation can be received in response to a change in a patientphysiological status. For example, the received information can indicatea change in, among other things, one or more of a patient activitylevel, a patient posture, a heart rate or respiratory rate, an intrinsicneural activity level, or an arrhythmia status.

In an example, at 801, information about a patient physiological statuscan be received from the physiological sensor 204. Upon receipt of theinformation, the processor circuit 110 can initiate delivery of theelectrical test signal at 810. Similarly, at 889, the processor circuit110 can receive physiological information from the same or a differentphysiological sensor. In response to receiving the physiologicalinformation, the processor circuit 110 can, at 890, initiate acalculation, diagnostic procedure, or therapy, such as an electricalneural modulation therapy.

In an example, the information about the patient physiological statusreceived at 801 or 889 can include patient physical activity statusinformation, such as including information from an accelerometercircuit, such as can be included in the system 100. In an example, thereceived patient physiological status information can include impedanceinformation, such as thoracic or cervical impedance information, such ascan be used to determine a patient respiratory status. In an example,the received information can include a blend of impedance informationand information from an accelerometer, such as to provide acomprehensive signal indicative of a patient's metabolic demand. In anexample, the comprehensive signal indicative of metabolic demand can beused, such as together with patient pulsatile information, to determineone or more neural modulation therapy parameters, such as can be used at890 to time delivery of an electrical neural modulation therapy.

In an example, the information about the patient physiological statusreceived at 801 or 889 can include intrinsic neural activityinformation. For example, an intrinsic neural activity signal can bedetected, such as using one or more electrodes disposed at or near nervetissue. In an example, intrinsic neural activity information can beinferred, such as using a patient physiological activity signal, such asa pulsatile signal or a baroreceptor activity signal. In an example, anintrinsic parasympathetic surge can occur in coordination with a peak ofa pulsatile signal waveform. At 890, an electrical neural modulationtherapy can be provided, such as in coordination with the detectedintrinsic neural activity to augment a patient's intrinsic neuralactivity, such as to augment an intrinsic parasympathetic surge. In anexample, a characteristic of the intrinsic neural activity signal can beused to trigger or adjust a neural modulation therapy parameter.

In an example, information about other activity of the IMD 105 can beused to indicate or adjust a neural modulation therapy parameter. Forexample, the processor circuit 110 can be configured to time delivery ofan electrical neural modulation therapy in coordination with arefractory period, or blanking period, of a portion of the IMD 105. Inan example, the IMD 105 can be configured to deliver electrostimulationto cardiac muscle tissue. During a blanking period when the IMD 105 isnot delivering electrostimulation to the cardiac muscle tissue (e.g.,during a cardiac refractory period), the IMD 105 can be configured toprovide the electrical neural modulation therapy. In an example,coordinating delivery of a neural modulation therapy with a blankingperiod of the IMD 105 can help avoid a therapy collision, or can helpavoid artifacts, such as within a patient body, that a portion of theIMD 105 may view as unusual or unexpected physiological behavior.

FIG. 9 illustrates generally an example that can include adjusting aneural modulation therapy parameter or providing an electrical neuralmodulation therapy. In an example, at 960, a pulsatile signal can bedetermined, such as according to the discussion at 860. At 980, one ormore pulsatile signal characteristics can be identified, such asaccording to the discussion at 880. At 985, one or more neuralmodulation therapy parameters can be adjusted. For example, one or moreneural modulation therapy parameters can be adjusted using informationabout a pulsatile signal characteristic identified at 980. Among otherplaces in this document, adjusting a neural modulation therapy parameteris described above, such as in the discussion of FIG. 3 or FIG. 4. In anexample, a neural modulation therapy timing parameter can be adjusted at985 using information about the pulsatile signal characteristicidentified at 980. For example, a therapy delay time can be eliminatedsuch that, at 990, an electrical neural modulation therapy can beprovided as soon as possible after identification of a particularpulsatile signal characteristic at 980 by the processor circuit 110.

In an example, at 985, a neural modulation therapy parameter, such ascan be used to determine an amplitude, frequency, duration, timing, orother characteristic of a neural modulation therapy pulse, can beadjusted using the processor circuit 110, such as in response to one ormore pulsatile signal characteristics identified at 980. In an example,at 990, an electrical neural modulation therapy can be provided, such asto a neural target, using the adjusted neural modulation therapyparameter.

At 901, physiological status information can be received from aphysiological sensor, such as the physiological sensor 204. In anexample, the physiological status information can be received accordingto the discussion at 801 or 889. In an example, at 985, the receivedphysiological status information can be used to adjust a neuralmodulation therapy parameter. In an example, at 985, at least one of thereceived physiological status information or the identified pulsatilesignal characteristic (e.g., identified at 980) can be used to adjust aneural modulation therapy parameter.

In an example, at 901, the received physiological status information caninclude information about a patient posture status. The postureinformation can be used, such as together with a pulsatile signalcharacteristic, to time delivery of a neural modulation therapy at 990.In an example, the processor circuit 110 can receive the postureinformation and can correspondingly adjust one or more neural modulationtherapy parameters.

In an example, posture information, such as can be received at 901, canbe used to determine the pulsatile signal at 960. Patient posture canhave an effect on blood vessels, such as cervical blood vessels, whichcan change shape (e.g., such as can significantly collapse or distend)in response to a patient posture change. Accordingly, cervical impedancemeasurements can vary widely depending on patient posture, such as whena patient is upright or lying down. In an example, a cervical bloodvessel can become engorged, such as when a patient lies down. Because ofthe engorgement, when the patient is lying down, the patient's cervicalimpedance can be substantially lower than when the patient is upright.Accordingly, at 960, the processor circuit 110 can compensate for suchcervical impedance changes by adjusting a baseline cervical impedance orby adjusting a pulsatile signal waveform.

In an example, posture information, such as can be received at 901, canbe used to initiate, terminate, or adjust a neural modulation therapy.For example, a particular neural modulation therapy (e.g., a neuralmodulation therapy defined at least in part by a particular neuralmodulation therapy parameter) can be configured to be delivered when apatient is at rest or sleeping. The processor circuit 110 can useposture information to detect when the patient is lying down for anextended period of time, and, when detected, the processor circuit 110can initiate or adjust a neural modulation therapy.

In an example, the pulsatile signal determined at 960, such as using thephysiological information received at 901, can be used to provide otherpatient health status information, such as can be used to determine oneor more neural modulation therapy parameters. For example, a change in apatient pulsatile signal, such as with or without a corresponding changein the received physiological status information, can indicate a changein a patient health status. For example, a patient health status changecan be indicated when a reduction in a pulsatile signal amplitude occursin the absence of a corresponding change in the patient's posture (e.g.,determined using physiological posture information received at 901). Inan example, an electrical neural modulation therapy can be provided inresponse to a patient health status change.

A neural modulation therapy parameter can be adjusted using informationabout a previously-delivered neural modulation therapy. For example, anaverage neural modulation therapy dosage can be determined, such as overa preceding interval (e.g., an hour, a week, etc.). To maintain a neuralmodulation therapy dosage, one or more neural modulation therapyparameters can be adjusted at 985.

FIG. 10 illustrates generally an example that can include detectingcardiac activity. In an example, at 1060, a pulsatile signal can bedetermined, such as according to the discussion at 860. At 1080, apulsatile signal feature can be identified, such as according to thediscussion at 880.

At 1022, a cardiac activity signal can be detected. A cardiac activitysignal can be determined in numerous ways, including using informationabout cardiac electrical activity, such as can be obtained using one ormore electrodes coupled to the IMD 105, such as using the implantablelead system 108. A cardiac activity signal can be determined using othermeans, such as acoustically using heart sounds, mechanically using apressure sensor, or as described above using cervical impedance. In anexample, a cardiac activity signal can include an ECG signal, or othersignal, such as a heart sound signal from which a cardiac activitysignal can be inferred or determined.

At 1082, a cardiac activity signal characteristic can be identified. Inan example, any signal characteristic can be used, such as including,among others, a timing, amplitude, frequency, shape, or integral of aportion of the cardiac activity signal. In an example, a sum,difference, linear combination, or product of identified cardiacactivity signal characteristic can be used. In an example, at 1082, theprocessor circuit 110 can be used to identify at least onecharacteristic of the cardiac activity signal. Similarly, at 1080, theprocessor circuit 110 can optionally be used to identify at least onepulsatile signal characteristic. In response to the identified at leastone characteristic, the processor circuit 110 can optionally adjust aneural modulation therapy parameter, or, at 1090, provide an electricalneural modulation therapy, such as using an adjusted neural modulationtherapy parameter. In an example, information about cardiac activity canbe used, such as together with a pulsatile signal characteristic, totime delivery of a neural modulation therapy.

In an example, a lower heart rate limit (LRL) can be used to modulatethe electrical neural modulation therapy provided at 1090. In someexamples, neural modulation therapy can reduce a patient heart rate. Ifa patient heart rate approaches or exceeds a LRL, a neural modulationtherapy can be ceased or adjusted to avoid further reducing the heartrate. For example, if the detected cardiac activity at 1022 indicatesthat a patient heart rate has fallen below the LRL, a neural modulationtherapy parameter can be adjusted, such as to terminate or adjustdelivery of an electrical neural modulation therapy. Similarly, amaximum tracking rate (MTR) can be used to modulate the electricalneural modulation therapy provided at 1090. For example, if a patientheart rate approaches or exceeds the MTR, a neural modulation therapycan be terminated or adjusted. In an example, parameters associated withpacemaker therapy (e.g., LRL, MTR, etc.) can be received from animplanted pacemaker that can be separate from the IMD 105, or from apacemaker therapy unit contained within the IMD 105.

FIG. 11 illustrates generally an example that can include trendinginformation about a pulsatile signal. At 1160, a pulsatile signal can bedetermined, such as according to the discussion at 860. At 1180, apulsatile signal feature can be identified, such as according to thediscussion at 880. At 1183, information about the pulsatile signal canbe trended.

The information trended about the pulsatile signal at 1183 can include,for example, one or more pulsatile signal characteristics, orrelationships between characteristics, such as between characteristicsof a pulsatile signal and characteristics of another physiologicalsignal. For example, a relationship between a pulsatile signalcharacteristic and a thoracic impedance signal characteristic can betrended. FIG. 13 illustrates several examples of information trendedabout a relationship between a pulsatile signal and an ECG signal. FIG.12 illustrates several examples of information trended aboutcharacteristics of a pulsatile signal.

Returning to FIG. 11, at 1191, patient health status information can beprovided, such as using the trended information about the pulsatilesignal. In an example, the patient health status information can beprovided to the patient, such as using various alerts emitted by the IMD105, or using a device interface (e.g., using the external module 115).In an example, the patient health status information can be communicatedto a caregiver, or the information can be stored, such as locally orexternally, for later or concurrent processing, such as in a remotepatient management system. In an example, the patient health statusinformation provided at 1191 can include information about a change inthe patient's pulsatile activity over time, such as to indicate aneffectiveness of neural modulation therapy.

At 1185, a neural modulation therapy parameter can be adjusted, such asusing the trended information about the pulsatile signal. For example,if the trended information indicates a patient status change by morethan a threshold amount, a neural modulation therapy parameter can beadjusted, such as to increase an amplitude or a frequency of a neuralmodulation therapy signal. At 1190, an electrical neural modulationtherapy can be provided to the patient, such as using the adjustedneural modulation therapy parameter.

FIG. 12 illustrates generally an example of trended information about apulsatile signal. The example of FIG. 12 can include a chart 1200, suchas including one or more pulsatile information trendlines. In anexample, the chart 1200 can include a first pulsatile signal trendline1201, such as can indicate a pulsatile signal magnitude trend. Thepulsatile signal magnitude information can be normalized, such as shownin the example of FIG. 12. In an example, the x axis of the chart 1200can represent discrete time intervals, such as corresponding toindividual physiological cycles (e.g., a cardiac cycle), or otherperiods. For example, the first pulsatile signal trendline 1201 canrepresent pulsatile signal magnitude that has been recorded and trended,such as corresponding to a series of patient physiological cycles. In anexample, the x axis can represent longer intervals. In an example, acentral tendency of the pulsatile signal magnitude information can berecorded and trended, such as corresponding to hourly, daily, or weeklytendencies. In an example, an average of pulsatile signal magnitudeinformation, such as over the course of an hour, can be recorded andtrended, such as over the course of several hours.

In an example, the first pulsatile signal trendline 1201 can be used bythe processor circuit 110 or a caregiver to recognize a change in apatient's health 301 status, such as over a period of time. In theexample of FIG. 12, a decreasing pulsatile signal magnitude can beobserved.

In an example, the chart 1200 can include additional trendlines, such asa second pulsatile signal trendline 1202. In an example, the secondpulsatile signal trendline 1202 can indicate a pulse pressure durationat half-maximum (e.g., the time interval Δt_((1/2)MAX) illustrated inthe example of FIG. 4). In an example, the first and second pulsatilesignal trendlines 1201 and 1202 can correspond to the same or differentintervals, such as along the x axis of the chart 1200. In the example ofFIG. 12, the pulse pressure duration at half-maximum increases over thetrended period. In an example, information about one or more of thefirst and second trendlines 1201 and 1202 can be used to provide anindication of a patient health status (e.g., at 1191), or can be used toadjust a neural modulation therapy parameter (e.g., at 1185). In anexample, the processor circuit 110 can be configured to interpretinformation about a pulsatile trend using additional informationreceived from a physiological sensor, such as a patient heart ratesensor or posture sensor, such as to calibrate, adjust, or disregard apulsatile signal trend. For example, during periods of transitionbetween patient postures, pulsatile signal trend information can bedisregarded.

FIG. 13 illustrates generally an example of trended information about apulse pressure signal. In an example, a pulse pressure signal can bedetermined using a patient pulsatile signal. The example of FIG. 13 caninclude a chart 1300, such as including one or more pulse pressuretrendlines. In an example, the chart can indicate a change in a pulsepressure characteristic interval, such as corresponding to a particulartime interval along the x axis. In an example, the time interval caninclude a particular physiological cycle (e.g., a cardiac cycle), orsome other time duration (e.g., a minute, a week, etc.). In an examplewhere the time interval includes a particular or individualphysiological cycle, the characteristic interval information cancorrespond to that physiological cycle. In an example where the timeinterval includes some other, longer duration, a central tendency orother indication of characteristic interval information over time can beused.

In an example, a third trendline 1303 can indicate a relationship overtime of an interval between a detected R-wave peak and a correspondingpulse pressure peak (see, e.g., FIG. 3 at 311 and 331). That is, thethird trendline 1303 can indicate a relationship or association betweena cardiac electrical event and a pulse pressure, such as pulse pressurein a vessel distal to the heart. In an example, a neural modulationtherapy parameter can be adjusted in response to a change in the thirdtrendline 1303. For example, when the third trendline 1303 exceeds athreshold 1313 (e.g., in the example of FIG. 13, on or after time 13), aneural modulation therapy parameter can be adjusted, such as accordingto the discussion at 985 or 1185. In an example, information about apatient health status can be provided in response to changes in thethird trendline 1303. For example, when the third trendline 1303 exceedsthe threshold 1313, the information about the patient health status canbe provided, such as according to the discussion at 1191.

The example of FIG. 13 can include a fourth trendline 1304, such as canindicate a relationship between relative characteristics of a pulsepressure signal. For example, the fourth trendline 1304 can includeinformation about an interval between a pulse pressure thresholdcrossing and a pulse pressure peak, such as over a particularphysiological cycle. As illustrated in FIG. 4, the interval can bebetween a pulsatile signal peak and a crossing of the pulsatile signalthreshold 332 (e.g., the interval Δt₄ in FIG. 4).

In an example, a neural modulation therapy parameter can be adjusted inresponse to changes in the fourth trendline 1304. For example, when thefourth trendline 1304 indicates a change of more than threshold intervalover a particular time window, a neural modulation therapy parameter canbe adjusted, such as according to the discussion at 985 or 1185. Forexample, when the interval between the pulse pressure threshold crossingand the pulse pressure peak changes by more than about 0.75 ms, such asover fewer than five time intervals, a neural modulation therapyparameter can be adjusted or an electrical neural modulation therapy canbe provided, or both. In an example, information about a patient healthstatus can be provided in response to changes in the fourth trendline1304. Additional information about a patient health status can beprovided using other trends, such as comprising information about pulsepressure signal characteristics, pulsatile signal characteristics, orother physiological signal characteristics.

One of ordinary skill in the art will understand that software,hardware, firmware, or combinations thereof, can be used to implementthe present subject matter. Method examples described herein can bemachine or computer-implemented at least in part. Some examples caninclude a computer-readable medium or machine-readable medium encodedwith instructions operable to configure an electronic device to performmethods as described in the above examples. An implementation of suchmethods can include code, such as microcode, assembly language code, ahigher-level language code, or the like. Such code can include computerreadable instructions for performing various methods. The code may formportions of computer program products. Further, in an example, the codecan be tangibly stored on one or more volatile, non-transitory, ornon-volatile, tangible computer-readable media, such as during executionor at other times. Examples of these tangible computer-readable mediacan include, but are not limited to, hard disks, removable magneticdisks, removable optical disks (e.g., compact disks and digital videodisks), magnetic cassettes, memory cards or sticks, random accessmemories (RAMs), read only memories (ROMs), and the like.

The above detailed description is intended to be illustrative and notrestrictive. Other embodiments will be apparent to those of skill in theart upon reading and understanding the above description. The scope ofthe invention should, therefore, be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled.

The claimed invention is:
 1. A method comprising: detecting fluctuationsin a cervical vessel dimension of a patient, wherein detecting thefluctuations includes measuring a cervical impedance of the patient overtime; determining pulsatile information using the detected fluctuationsin the cervical vessel dimension of the patient; and providing a neuralmodulation therapy coordination with a characteristic of the pulsatileinformation.
 2. The method of claim 1, wherein the providing the neuralmodulation therapy includes providing an electrical neural modulationtherapy in coordination with the characteristic of the pulsatileinformation.
 3. The method of claim 2, wherein the providing theelectrical neural modulation therapy includes providing the electricalneural modulation therapy at or near a cervical neural target includingat least one of a vagus nerve, a carotid sinus nerve, a hypoglossalnerve, a glossopharyngeal nerve, and a phrenic nerve.
 4. The method ofclaim 2, wherein the providing the electrical neural modulation therapyincludes providing the electrical neural modulation therapy to modulateneural activity in a nerve that innervates one or more baroreceptors. 5.The method of claim 2, wherein the providing the electrical neuralmodulation therapy includes providing the electrical neural modulationtherapy to modulate neural activity in a nerve that innervates one ormore chemoreceptors.
 6. The method of claim 2, wherein the providing theelectrical neural modulation therapy includes providing the electricalneural modulation therapy to modulate neural activity in a spinal neuraltarget, including in one of a cervical, thoracic, lumbar, or sacralspinal region.
 7. The method of claim 2, wherein the providing theelectrical neural modulation therapy includes providing the electricalneural modulation therapy to modulate neural activity in a cardiac nerveor cardiac fat pad.
 8. The method of claim 2, wherein the providing theelectrical neural modulation therapy includes providing the electricalneural modulation therapy to modulate neural activity in a renal nerve.9. The method of claim 1, further comprising adjusting a neuralmodulation therapy parameter in response to an identified characteristicof the pulsatile signal, and wherein the providing the neural modulationtherapy includes using the adjusted neural modulation therapy parameter.10. The method of claim 1, further comprising receiving informationabout the patient's heart rate; wherein the providing the neuralmodulation therapy includes in coordination with the characteristic ofthe pulsatile information and using the information about the patient'sheart rate.
 11. The method of claim 1, further comprising receiving anindication of a patient's posture from a posture detection circuit;wherein the providing the neural modulation therapy includes incoordination with the characteristic of the pulsatile information andusing the indication of the patient's posture.
 12. The method of claim1, further comprising: identifying a peak time using the pulsatileinformation; and adjusting the neural modulation therapy using anadjustable delay and the identified peak time.
 13. The method of claim1, wherein the providing the neural modulation therapy includesproviding an autonomic neural modulation therapy to the patient incoordination with the patient's intrinsic neural activity.
 14. Themethod of claim 1, further comprising: receiving cardiac activityinformation from the patient; and identifying a cardiac refractoryperiod in the received cardiac activity information; wherein theproviding the neural modulation therapy includes providing the neuralmodulation therapy to the patient in coordination with the identifiedcardiac refractory period.
 15. The method of claim 1, wherein thedetermining the pulsatile information using the detected fluctuations inthe cervical vessel dimension of the patient includes determining apulse pressure signal; and wherein the providing the neural modulationtherapy includes in coordination with a characteristic of the pulsepressure signal.
 16. A method comprising: detecting fluctuations in acervical vessel dimension of a patient, wherein detecting thefluctuations includes measuring a cervical impedance of the patient overtime; determining a pulsatile signal based on the detected fluctuationsin the cervical vessel dimension of the patient; identifying a patientphysiological cycle; and providing a neural modulation therapy incoordination with the identified patient physiological cycle, wherein aparameter of the neural modulation therapy is determined in part using afirst characteristic of the pulsatile signal.
 17. The method of claim16, wherein the identifying the patient physiological cycle includesusing a different second characteristic of the determined pulsatilesignal to identify a portion of the patient physiological cycle.
 18. Themethod of claim 16, wherein the identifying the patient physiologicalcycle includes identifying a portion of a cardiac cycle using a measuredcardiac activity signal.
 19. The method of claim 16, further comprisingidentifying the first characteristic of the pulsatile signal, the firstcharacteristic including at least one of: an amplitude of the pulsatilesignal; a frequency determined using the pulsatile signal; a shape ofthe pulsatile signal; an integral of a portion of the pulsatile signal;a derivative of a portion of the pulsatile signal; a ratio ofcharacteristics derived from the pulsatile signal; or a sum, difference,linear combination, or product of characteristics derived from thepulsatile signal.
 20. A medical device for controlling at least aportion of a neural modulation therapy, the device comprising: adetector circuit configured to detect cervical impedance of a patientand generate a cervical impedance signal representing fluctuations inthe detected cervical impedance over time; a therapy delivery circuitconfigured to provide neural modulation therapy to the patient using aneural modulation therapy timing parameter, the timing parametercorresponding to a specified portion of a physiologic cycle of thepatient; and a processor circuit, coupled to the detector circuit andthe therapy delivery circuit, the processor circuit configured to:determine a pulsatile signal using the cervical impedance signal;identify at least one characteristic of the pulsatile signal; andcontrol delivery of the neural modulation therapy using the neuralmodulation therapy timing parameter and the at least one identifiedcharacteristic of the pulsatile signal.